Nitrogen monoxide (NO) regulates numerous physiological processes, inter alia neurotransmission, relaxation and proliferation of the smooth musculature, adhesion and aggregation of thrombocytes and tissue injury and inflammation. Because of the large number of signal functions, NO is associated with a number of diseases (see e.g. L. J. Ignarro, Angew. Chem. (1999), 111, 2002-2013 and F. Murad, Angew. Chem. Int. Ed. (1999), 111, 1976-(1999), 111, 2002-2013 and F. Murad, Angew. Chem. Int. Ed. (1999), 111, 1976-1989). The enzyme responsible for the physiological formation of NO, NO synthase (NOS), plays an important role here in the therapeutic influencing of these diseases. Three different iso-forms of NO synthase, namely the two constitutive forms nNOS and eNOS and the inducible form iNOS, have so far been identified (A. J. Hobbs, A. Higgs, S. Moncada, Annu. Rev. Pharmacol. Toxicol. (1999), 39, 191-220; I. C. Green, P.-E. Chabrier, DDT (1999), 4, 47-49; P.-E. Chabrier et al., Cell. Mol. Life Sci. (1999), 55, 1029-1035).
Inhibition of NO synthase opens up new therapy set-ups for various diseases connected with NO (A. J. Hobbs et al., Annu. Rev. Pharmacol. Toxicol. (1999), 39, 191-220; I. C. Green, P.-E. Chabrier, DDT (1999), 4, 47-49; P.-E. Chabrier et al., Cell. Mol. Life Sci. (1999), 55, 1029-1035), such as, for example, migraine (L. L. Thomsen, J. Olesen, Clinical Neuroscience (1998), 5, 28-33; L. H. Lassen et al., The Lancet (1997), 349, 401-402), septic shock, neurodegenerative diseases, such as multiple sclerosis, Parkinson's disease, Alzheimer's disease or Huntington's disease, inflammations, inflammation pain, cerebral ischaemia, diabetes, meningitis and arteriosclerosis. Furthermore, inhibition of NOS can have an effect on wound healing, on tumors and on angiogenesis, as well as effecting a non-specific immunity against microorganisms (A. J. Hobbs et al., Annu. Rev. Pharmacol. Toxicol. (1999), 39, 191-220).
Active compounds which inhibit NO synthase and are known to date are, in addition to L-NMMA and L-NAME—i.e. analogs of L-arginine, from which NO and citrulline are formed in vivo with involvement of NOS—inter alia S-methyl-L-citrulline, aminoguanidine, S-methylisourea, 7-nitroindazole and 2-mercaptoethylguanidine (A. J. Hobbs et al., Annu. Rev. Pharmacol. Toxicol. (1999), 39, 191-220).